Measures of postural steadiness are used to characterize the dynamics of the postural control system associated with maintaining balance during quiet standing. The objective of this study was to ...evaluate the relative sensitivity of center-of-pressure (COP)-based measures to changes in postural steadiness related to age. A variety of time and frequency domain measures of postural steadiness were compared between a group of twenty healthy young adults (21-35 years) and a group of twenty healthy elderly adults (66-70 years) under both eyes-open and eyes-closed conditions. The measures that identified differences between the eyes-open and eyes-closed conditions in the young adult group were different than those that identified differences between the eye conditions in the elderly adult group. Mean velocity of the COP was the only measure that identified age-related changes in both eye conditions, and differences between eye conditions in both age groups. The results of this study will be useful to researchers and clinicians using COP-based measures to evaluate postural steadiness.
A gradient free optimization-simulation method for processes modelled with the simulator Aspen HYSYS is developed. The tool is based on a Tabu Search (TS) and the Nelder-Mead Downhill Simplex (NMDS) ...method. The local optima that result from the TS are fine-tuned with NMDS to reduce the required number of simulations. The tool has been applied to find the total refrigerant flow rate, composition and the refrigerant suction and condenser pressures that minimize the energy requirements of a Prico process. The main strength of this method is that it has a high probability of obtaining a better solution with significantly fewer simulation runs than other metaheuristic methods. Also, by changing the TS step size it is possible to influence the initial search pattern, thereby taking advantage of already gained process knowledge to decrease the optimization time. The method is general and can be applied to other processes modelled in Aspen HYSYS.
Abstract Two-dimensional magnitude squared coherence (2D-MSC) is developed to compare the two-valued time series which represent the center of pressure (COP) under each foot. A sinusoidal multiple ...taper spectral estimator is used to reduce bias and improve spectral resolution. The measure is applied to evaluate symmetry in the dual-plate postural steadiness time series obtained from healthy young and elderly volunteers, and patients with Huntington's Disease (HD), a group in which asymmetries in postural steadiness are anticipated. The results demonstrate that the 2D-MSC is a robust measure of inter-limb coordination that may be of value in studies of aging and neurologic disease.
We consider a revenue management model for pricing a product line with several customer segments under the assumption that customers’ product choices are determined entirely by their reservation ...prices. We highlight key mathematical properties of the maximum utility model and formulate it as a mixed-integer programming problem, design heuristics and valid cuts. We further present extensions of the models to deal with various practical issues arising in applications. Our computational experiments with real data from the tourism sector as well as with the randomly generated data show the effectiveness of our approach.
The objective of this study was to develop a numerical solver to calculate the magneto-hydrodynamic (MHD) signal produced by a moving conductive liquid, i.e. blood flow in the great vessels of the ...heart, in a static magnetic field. We believe that this MHD signal is able to non-invasively characterize cardiac blood flow in order to supplement the present non-invasive techniques for the assessment of heart failure conditions. The MHD signal can be recorded on the electrocardiogram (ECG) while the subject is exposed to a strong static magnetic field. The MHD signal can only be measured indirectly as a combination of the heart's electrical signal and the MHD signal. The MHD signal itself is caused by induced electrical currents in the blood due to the moving of the blood in the magnetic field. To characterize and eventually optimize MHD measurements, we developed a MHD solver based on a finite element code. This code was validated against literature, experimental and analytical data. The validation of the MHD solver shows good agreement with all three reference values. Future studies will include the calculation of the MHD signals for anatomical models. We will vary the orientation of the static magnetic field to determine an optimized location for the measurement of the MHD blood flow signal.
Protein kinase C (PKC) is a family of serine/threonine protein kinases involved in many cellular responses. Although the analysis of PKC activity in many systems has provided crucial insights to its ...biologic function, the precise role of different isoforms on the differentiation of normal hematopoietic progenitor cells into the various lineages remains to be investigated. The authors have assessed the state of activation and protein expression of PKC isoforms after cytokine stimulation of CD34(+) progenitor cells from human bone marrow. Freshly isolated CD34(+) cells were found to express PKC-alpha, PKC-beta2, and PKC-epsilon, whereas PKC-delta, PKC-gamma, and PKC-zeta were not detected. Treatment with erythropoietin (EPO) or with EPO and stem cell factor (SCF) induced a predominantly erythroid differentiation of CD34(+) cells that was accompanied by the up-regulation of PKC-alpha and PKC-beta2 protein levels (11.8- and 2.5-fold, respectively) compared with cells cultured in medium. Stimulation with EPO also resulted in the nuclear translocation of PKC-alpha and PKC-beta2 isoforms. Notably, none of the PKC isoforms tested were detectable in CD34(+) cells induced to myeloid differentiation by G-CSF and SCF stimulation. The PKC inhibitors staurosporine and calphostin C prevented EPO-induced erythroid differentiation. Down-regulation of the PKC-alpha, PKC-beta2, and PKC-epsilon expression by TPA pretreatment, or the down-regulation of PKC-alpha with a specific ribozyme, also inhibited the EPO-induced erythroid differentiation of CD34(+) cells. No effect was seen with PKC-beta2-specific ribozymes. Taken together, these findings point to a novel role for the PKC-alpha isoform in mediating EPO-induced erythroid differentiation of the CD34(+) progenitor cells from human bone marrow. (Blood. 2000;95:510-518)
To evaluate patterns of successful gait strategy in Huntington disease (HD) at various stages of illness to improve fall avoidance and maintenance of independence.
Repeated measurements of gait ...kinematic parameters and joint performance during gait cycles of six HD patients compared to 30 age-matched controls.
A standard gait laboratory.
Six HD patients, rank-ordered for disease severity from minimal chorea to generalized dystonia, selected because they were ambulatory despite 3 to 17 years' disease duration. One patient was from a nursing home (walked with assistance) and five were living independently, either alone or with a working spouse who was the caregiver.
Standardized gait evaluations (retroreflective markers on standard bony landmarks) from five video angles, fed into digitizer to computer-generate joint angles and standard gait kinematic parameters.
Wide variability in gait kinematic parameters and joint interaction plots (phase plane and angle-angle plots) was observed between individuals and successive trials of the same limb, tending to increase with disease severity. Joint interaction plots show that random, highly variable distractions from planned trajectories are more apparent distally.
Chorea in HD does not appreciably affect the center of gravity during ambulation, and the consistency of gait profiles at heel strike shows that the ultimate target is achieved in each step despite random and frequent variability during the gait cycle.
Fractal and correlation dimensions have been computed for time series obtained from tests of balance (postural steadiness). Although these measures appear to be reliable and differentiate subject ...groups, it has become clear that random (noise) time series may have finite dimensions and appear to demonstrate dynamics characteristic of nonlinear systems. Consequently, it is necessary to apply a test to distinguish a time series with putative nonlinear dynamics from random noise. A simple predictor was utilized to compare center of pressure (COP) time series with surrogate data constructed to have similar time and frequency domain characteristics. It was found that the original time series was more predictable than the surrogate data, suggesting that the COP data is derived from a nonlinear system.
Recent research has emphasized the importance of the metabolic cluster, which includes glucose intolerance, dyslipidemia, and high blood pressure, as a strong predictor of the obesity-related ...morbidities and premature mortality. Fundamental to this association, commonly referred to as the metabolic syndrome, is the close interaction between abdominal fat patterning, total body adiposity, and insulin resistance. As the initial step in identifying major genetic loci influencing these phenotypes, we performed a genomewide scan by using a 10-centiMorgan map in 2,209 individuals distributed over 507 nuclear Caucasian families. Pedigree-based analysis using a variance components linkage model demonstrated a quantitative trait locus (QTL) on chromosome 3 (3q27) strongly linked to six traits representing these fundamental phenotypes logarithm of odds (lod) scores ranged from 2.4 to 3.5. This QTL exhibited possible epistatic interaction with a second QTL on chromosome 17 (17p12) strongly linked to plasma leptin levels (lod = 5.0). Situated at these epistatic QTLs are candidate genes likely to influence two biologic precursor pathways of the metabolic syndrome.
Checkpoint blockade can reverse T-cell exhaustion and promote antitumor responses. Although blocking the PD-1 pathway has been successful in Hodgkin lymphoma, response rates have been modest in ...B-cell non-Hodgkin lymphoma (NHL). Coblockade of checkpoint receptors may therefore be necessary to optimize antitumor T-cell responses. Here, characterization of coinhibitory receptor expression in intratumoral T cells from different NHL types identified TIGIT and PD-1 as frequently expressed coinhibitory receptors. Tumors from NHL patients were enriched in CD8
and CD4
T effector memory cells that displayed high coexpression of TIGIT and PD-1, and coexpression of these checkpoint receptors identified T cells with reduced production of IFNγ, TNFα, and IL2. The suppressed cytokine production could be improved upon
culture in the absence of ligands. Whereas PD-L1 was expressed by macrophages, the TIGIT ligands CD155 and CD112 were expressed by lymphoma cells in 39% and 50% of DLBCL cases and in some mantle cell lymphoma cases, as well as by endothelium and follicular dendritic cells in all NHLs investigated. Collectively, our results show that TIGIT and PD-1 mark dysfunctional T cells and suggest that TIGIT and PD-1 coblockade should be further explored to elicit potent antitumor responses in patients with NHL.
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